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Sleep and Circadian Rhythms in Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common cause of dementia. AD is clinically heterogeneous, with numerous risk factors that affect its clinical and neuropathologic course. The hallmark neuropathology of AD is the accumulation of extracellular deposits of amyloid beta (Aβ) and intraneuronal accumulation of hyperphosphorylated tau, which lead to neuronal cell death, brain atrophy, and severe cognitive impairment.

Sleep abnormalities have long been known to be a feature of neurodegenerative disorders and in some cases are considered a core manifestation of the disease. Sleep has been shown to directly regulate the rate of Aβ production and clearance from the brain, and evidence suggests that sleep disruption may be a direct critical pathway by which Aβ disrupts memory consolidation. Thus, improving sleep may directly support mnemonic processes and reduce the accumulation of Aβ, which is considered the pathogenic driver of AD.

Patients with AD also exhibit disruptions of daily (circadian) rhythms, but it is unclear whether this reflects a primary disorder of internal circadian timekeeping and whether disruption contributes to symptoms and progression. Circadian biology examines daily 24-hour (‘circa-diem’) rhythms that govern many aspects of physiology, behaviour and metabolism, including sleep-wake cycle, rest-activity patterns, cognitive function, mood, and many hormonal rhythms and metabolic processes. Changes in circadian rhythms may be a strong, reliable, and measurable indicator of the earliest signs of AD. Correction of circadian misalignment, including promotion of more stable and robust rhythms in cognition, sleep-wake, and metabolism, holds promise as an inexpensive and noninvasive method for slowing disease progression and improving quality of life for patients and their families.

To learn more, here is our recent review .

Related papers:

Kent, B. A., Feldman, H. H., Nygaard, H. B.  (2020). Sleep and its Regulation: An Emerging Pathogenic and Treatment Frontier in Alzheimer’s disease. Progress in Neurobiology

Kent, B. A., Michalik, M., Marchant, E. G., Yau, K. W., Feldman, H. H., Mistlberger, R. E., Nygaard, H. B. (2019). Delayed daily activity and reduced NREM slow wave power in the APP/PS1 mouse model of Alzheimer’s disease. Neurobiology of Aging, 78, 74-86.

Kent, B. A., Strittmatter, S. M., Nygaard, H. B. (2018). Sleep and EEG power spectral analysis in three transgenic mouse models of AD: APP/PS1, 3xTgAD, and Tg2576. Journal of Alzheimer’s Disease, 64(4), 1325-1336.

Kent, B. A., & Mistlberger, R. E. (2017). Sleep and hippocampal neurogenesis: implications for Alzheimer’s disease. Frontiers in Neuroendocrinology, 45, 35-52.

Kent, B. A. (2014). Synchronizing an aging brain: can entraining circadian clocks by food slow Alzheimer’s disease? Frontiers in Aging Neuroscience, 6, 234.